Anatomically specific reactive oxygen species production participates in Marfan syndrome aneurysm formation

Fabian Emrich1,2, Kiril Penov1,2, Mamoru Arakawa1,3

  • 1Department of Cardiothoracic Surgery, Stanford University, Stanford, California.

Insights

Reactive oxygen species (ROS) contribute to aortic aneurysm development in Marfan syndrome (MFS). Inhibiting ROS with apocynin reduced aneurysm growth and elastin breakdown in MFS mice.

Area of Science:

  • Cardiovascular Biology
  • Connective Tissue Disorders
  • Molecular Medicine

Background:

  • Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, leading to aortic root aneurysm.
  • The precise mechanism by which reactive oxygen species (ROS) contribute to aortic wall remodeling in MFS is not fully understood.

Purpose of the Study:

  • To investigate the role of ROS in the pathogenesis of aortic aneurysms in a mouse model of Marfan syndrome.
  • To explore the potential therapeutic effect of ROS inhibition on aneurysm progression.

Main Methods:

  • Analysis of aortic tissues from Marfan syndrome (Fbn1C1039G/+) and control mice using DHE staining, lucigenin-enhanced chemiluminescence (LGCL), and elastin Van-Gieson staining.
  • In situ zymography to assess protease activity and in vitro studies on smooth muscle cells (SMCs) treated with TGF-β antibody and angiotensin II (AngII).

Main Results:

  • ROS were detected in the ascending aorta of MFS mice during early aneurysm formation.
  • Treatment with apocynin, a NADPH oxidase inhibitor, reduced aneurysm formation and elastin fragmentation in MFS mice.
  • Angiotensin II (AngII) increased ROS production in MFS aortic SMCs in a TGF-β-dependent manner.

Conclusions:

  • ROS play a significant role in the development and progression of aortic aneurysms in Marfan syndrome.
  • Inhibition of ROS, for example, via apocynin, can attenuate aneurysm development.
  • Angiotensin II contributes to ROS production in MFS aortic smooth muscle cells, suggesting a potential therapeutic target.

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